The adenomatous polyposis coli protein unambiguously localizes to microtubule plus ends and is involved in establishing parallel arrays of microtubule bundles in highly polarized epithelial cells
The adenomatous polyposis coli protein unambiguously localizes to microtubule plus ends and is involved in establishing parallel arrays of microtubule bundles in highly polarized epithelial cells
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DOI：
10.1083/jcb.200203001
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发表时间：
2002-06-10
影响因子：
7.8
通讯作者：
Näthke, IS
中科院分区：
文献类型：
--
作者：
Mogensen, MM;Tucker, JB;Näthke, IS
在家族性和散发性病例中，全长腺瘤性结肠息肉病（APC）蛋白的缺失与结肠癌的发生相关。除了在Wnt信号通路中调节β-连环蛋白水平的作用外，APC蛋白还参与调节细胞骨架组织。APC在体内和体外稳定微管，这可能在细胞迁移中起作用（Nathke，I.S.，C.L.放大图片作者：亚当斯，P.塞尔林和W. J.纳尔逊。1996. J. Cell Biol.134：165-179; Mimori-Kiyosue，Y.，N. Shiina和S.月田2000. J. Cell Biol.148：505-517; Zumbrunn，J.，K. Inoshita，A.A.海曼和I.S.纳特克2001. Curr. 11：44-49）和在有丝分裂期间微管与动粒的附着中（Fodde，R.，J. Kuipers，C.罗森伯格河Smits，M.基尔曼角加斯帕，J.H.货车埃斯角作者：J. Giles和H.聪明人2001. Nat.CellBiol.3：433-438; Kaplan，K.B.，A. Burds，J.R. Swedlow，S.S.贝基尔峰Sorger和I.S.纳特克2001. 3：429-432）。内源性APC蛋白的定位是复杂的：已经在培养的细胞中鉴定了APC的肌动蛋白和微管依赖性库（Nathke et al.，1996; Mimori-Kiyosue等人，2000; Reinacher-Schick，A.，和B.M.之间的关系。甘比纳。2001. J. Cell Biol.152：491-502; Rosin-Arbesfeld，R.，G. Ihrke和M.欢迎2001. EMBO J. 20：5929-5939）。然而，APC在组织中的定位尚未在高分辨率下确定。在这里，我们表明，在完全极化的上皮细胞从内耳，内源性APC蛋白与微管位于基底质膜的正端。与APC在体内支持上皮细胞的细胞骨架组织中的作用一致，从APC杂合子小鼠中分离的微管束的顶端-基底阵列中微管的数量显著减少。
Loss of full-length adenomatous polyposis coli (APC) protein correlates with the development of colon cancers in familial and sporadic cases. In addition to its role in regulating beta-catenin levels in the Wnt signaling pathway, the APC protein is implicated in regulating cytoskeletal organization. APC stabilizes microtubules in vivo and in vitro, and this may play a role in cell migration (Nathke, I.S., C.L. Adams, P. Polakis, J.H. Sellin, and W.J. Nelson. 1996. J. Cell Biol. 134:165-179; Mimori-Kiyosue, Y., N. Shiina, and S. Tsukita. 2000. J. Cell Biol. 148:505-517; Zumbrunn, J., K. Inoshita, A.A. Hyman, and I.S. Nathke. 2001. Curr. Biol. 11:44-49) and in the attachment of microtubules to kinetochores during mitosis (Fodde, R., J. Kuipers, C. Rosenberg, R. Smits, M. Kielman, C. Gaspar, J.H. van Es, C. Breukel, J. Wiegant, R.H. Giles, and H. Clevers. 2001. Nat. Cell Biol. 3:433-438; Kaplan, K.B., A. Burds, J.R. Swedlow, S.S. Bekir, P.K. Sorger, and I.S. Nathke. 2001. Nat. Cell Biol. 3:429-432). The localization of endogenous APC protein is complex: actin- and microtubule-dependent pools of APC have been identified in cultured cells (Nathke et al., 1996; Mimori-Kiyosue et al., 2000; Reinacher-Schick, A., and B.M. Gumbiner. 2001. J. Cell Biol. 152:491-502; Rosin-Arbesfeld, R., G. Ihrke, and M. Bienz. 2001. EMBO J. 20: 5929-5939). However, the localization of APC in tissues has not been identified at high resolution. Here, we show that in fully polarized epithelial cells from the inner ear, endogenous APC protein associates with the plus ends of microtubules located at the basal plasma membrane. Consistent with a role for APC in supporting the cytoskeletal organization of epithelial cells in vivo, the number of microtubules is significantly reduced in apico-basal arrays of microtubule bundles isolated from mice heterozygous for APC.